Antiemetics
Ondansetron hydrochloride is an antiemetic ondansetron hydrochloride. Its pharmacological effects is similar with ondansetron, and ondansetron hydrochloride is a potent, highly selective 5-HT3 receptor antagonist, which has a strong antiemetic effect of chemotherapy, radiotherapy and post-operative nausea effect, that is better than metoclopramide.
Ondansetron, granisetron, and dolasetron are three common clinical antiemetic. Ondansetron is an effective, reversible and selective serotonin (5-HT3) blocker. It have little effect for α1, α2, β1, β2-adrenergic receptor and the histamine H1, H2 receptor, which have minimal effect on H receptors, central and peripheral dopaminergic receptor antagonistic effect. It can be suppressed by the chemotherapy and radiotherapy-induced nausea and vomiting. Compared with metoclopramide, it has strong antiemetic effect without extrapyramidal reactions. Vomiting induced by cisplatin, cyclophosphamide, doxorubicin, etc. can produce rapid and strong antiemetic effect. Suitable for the treatment of nausea and vomiting, nausea, vomited by the cytotoxic chemotherapy and radiation therapy. It can also prevent and treat nausea and vomit induced by surgically .
Ondansetron, as a transit point in the gastrointestinal tract visceral afferent nerve activation and vomiting center within the spinal cord between the diaphragm and abdominal muscles, makes it happen in abdominal muscles and diaphragm movement. Chemotherapy and radiation therapy can cause intestinal 5-HT to release. It can be caused by 5-HT3 receptor vagus nerve that cause vomiting reflex. This product block this reflex occurs at the same time of blocking the action by the central trigger vomiting. The role of postoperative nausea and vomiting mechanism is unknown. Ondansetronin, in combination with dexamethasone, can enhance the antiemetic effect.
Dosage
Ondansetron hydrochloride is mainly used to control nausea and vomiting after the cytotoxic chemotherapy, adiotherapy and surgery.
For highly emetic chemotherapy: adult can slow static note 8 mg before chemotherapy or static drops, then can be 1 mg per 1 hours drop 24 hours later; it can also slow intravenous infusion interval 4 hours or static drops 8 mg 2 times. After every 8 hours of oral 4mg, once every 5 days. Children aged 4 within 15 min prior to chemotherapy static drop 5 mg/m2, then every 8 hours of oral 4 mg, Ed. 5
Nausea and vomiting caused by the factors of prevention or treatment of surgery: Adult dose is 4 mg each time, before the induction of anesthesia or symptoms to intramuscular injection or slow static note.
Radiation-induced vomiting: course of treatment can be controlled by the course of radiotherapy, mostly administered orally.
Intravenous injection or intravenous drip, 0.9% sodium chloride, 5% dextrose, compound sodium chloride, 10% mannitol injection as a diluent solvent.
Description
Ondansetron hydrochloride is a selective 5HT3-antagonist approved for the management
of nausea and vomiting induced by cancer chemotherapy and radiotherapy. It is reported
to have a superior side-effect profile compared with metoclopramide, representing an
important advance in the treatment of nausea and vomiting associated with chemotherapy.
Ondansetron hydrochloride is the first specific 5HT3-antagonist to reach the market. It is
also under investigation for a number of other indications, including anxiety and
schizophrenia.
Chemical Properties
White or almost white powder.
Originator
Glaxo (United Kingdom)
Uses
A serotonin type 3 receptor antagonist.
Uses
Antiemetic;Serotonergic receptor antagonist
Uses
These Secondary Standards are qualified as Certified Reference Materials. These are suitable for use in several analytical applications including but not limited to pharma release testing, pharma method development for qualitative and quantitative analyses, food and beverage quality control testing, and other calibration requirements.
Uses
Ondansetron hydrochloride dihydrate has been used as a 5-HT
3 antagonist to attenuate rostro ventromedial medulla (RVM)/cholecystokinin (CCK)-induced mechanical hypersensitivity and to block the effects of trichostatin A (TSA) on 5-HT
3 protein.
Definition
ChEBI: Ondansetron hydrochloride is a member of carbazoles.
Manufacturing Process
Preparation of 3-ethoxalyl-9-methyl-1,2,3,9-tetrahydro-4H-carbozol-4-one
3.0 g (0.13 mole) of sodium metal are portionwise added to a stirred mixture containing 19.93 g (0.1 mole) of 9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4one, 19.0 g (0.13 mole) of diethyl oxalate, 2 g of ethanol and 200 ml of dioxane. The slightly warming reaction mixture is stirred at 40° to 50°C for 4 hours, then 16 g of glacial acetic acid and finally 200 ml of water are added thereto at room temperature. After filtering off the yellow crystalline suspension, the precipitate is washed with water and dried to give the title compound in a yield of 24 g (80.2%), m.p. 118°-120°C
Preparation of 3-hydroxymethyl-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4one-3-glyoxylic acid lacton
After adding 0.1 g of triethylamine to a stirred suspension containing 3.00 g (0.01 mole) of the 3-ethoxalyl-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4
2512 one, in 20 ml of acetone, 1.13 g (0.015 mole) of formol solution are dropwise added to the mixture. The suspension becomes clear within 1 to 2 minutes and crystals begin to precipitate. After further stirring at 35° to 40°C for one hour, the reaction mixture is cooled down to room temperature, filtered off, the precipitate is washed with 50% acetone and dried to give 2.10 g (74.2%) of the title compound, m.p. 242°-244°C.
Preparation of ondansetron base (chemically 9-methyl-3-[(2-methyl-1-Himidazol-1-yl)methyl]-1,2,3,9-tetrahidro-4-H-carbazol-4-one)
A mixture containing 2.83 g (0.01 mole) of 3-hydroxymethyl-9-methyl-2,3,9tetrahydro-4H-carbazol-4-one-3-glyoxylic acid lactone, 15 ml of dioxane, 1.32 g of triethylamine, 1.0 g of ethanol and 1.64 g (0.02 mole) of 2methylimidazole is boiled under reflux while stirring for 5 hours. Thereafter, the reaction mixture is diluted with 45 ml of water and cooled down. The precipitate is filtered off, washed with aqueous dioxane and dried to obtain 2.56 g (87.3%) of the title compound, m.p. 220°-223°C.
Preparation of 9-methyl-3-[(2-methyl-1-H-imidazol-1-yl)methyl]-1,2,3,9tetrahydro-4H-carbazol-4-one hydrochloride dihydrate The process above described is followed, except that after cooling down the reaction mixture to room temperature after boiling, 20 ml of 37% aqueous hydrochloric acid are added thereto. Then, the precipitate is filtered off, washed with isopropanol and dried to obtain 2.40 g (65.6%) of the title salt, m.p. 178°-180°C. The active agent content of the product was found to be 100.3% based on potentiometric titration with sodium hydroxide solution. The theoretical water content is 9.85% (calculated for C18H19N3OHCl2H2O).The water content measured is 10.03%.
brand name
Zofran
(GlaxoSmithKline);Zophran.
Therapeutic Function
Serotonin antagonist
General Description
Ondansetron Hydrochloride acts as a 5HT3 (serotonin) antagonist and is a powerful antiemetic drug. It is widely used for the prevention and treatment of nausea and vomiting related to post-operative states, cancer chemotherapy and radiotherapy, and chronic medical illness. It has been found to exhibit inconsistent bioavailability resulting from its poor aqueous solubility and high first-pass hepatic metabolism.
Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.
Biological Activity
Selective 5-HT 3 receptor antagonist (K i = 6.16 nM). Antiemetic; prevents emesis induced by cytotoxic drugs and radiation.
Biochem/physiol Actions
5-HT3 serotonin receptor antagonist
Synthesis
Ondansetron hydrochloride W/O microemulsions were obtained by mixing candesartan cilexetil into a mixture of oleic acid, Tween 80 and isopropyl alcohol, then adding distilled water dropwise under vigorous stirring until the system turned transparent[1].
References
[1]Malakar, J., Nayak, A. K., & Basu, A. (2012). Ondansetron HCl Microemulsions for Transdermal Delivery: Formulation and In Vitro Skin Permeation. ISRN Pharmaceutics, 2012, 1–6.
https://doi.org/10.5402/2012/428396
